The mechanism of stimulus-response coupling mediated by Ca2+ was studied at three levels: the modulation of the Ca2+ signa 1 by calmodulin, the regulation of the Ca2+ and calmodulin-stimulated protein phosphatase, calcineurin, and the role of protein dephosphorylation in the control of mitosis. 1) We reported earlier that occupancy of two of the four Ca2+ sites of calmodulin destabilizes the hinge in the central helix of calmodulin between residues 74 to 77. Formation of a complex of calmodulin with a calmodulin-binding peptide changes the same residues from an alpha-helical to an extended conformation. Thus , Ca2+-induced changes in the central helix may facilitate the interaction of calmodulin with its targets. 2) Calcineurin was shown to contain high affinity Ca2+ sites saturated at resting Ca2+ levels and low affinity sites responsible for the small, calcineurin B-mediated, activation of the phosphatase activity at micromolar Ca2+ concentrations. At physiological Ca2+ levels in stimulated cells (0.5-1 'PM), the Ca2+-dependence of the large cooperative activation of calcineurin is dependent on calmodulin concentration. 3) The inactivation of the mitosis-specific cdc2 kinase accompanying the metaphase to telophase transition has been investigated by Dr. Suprynowicz. It is ATP-dependent, okadaic acid sensitive and mediated by at least two factors, one of them expressed specifically at telophase. These results suggest that the concerted action of a protein kinase and a phosphatase is responsible for switching off cell division during mitosis.